tbuckley/cabot-search huggingface dataset:
Airway clearance techniques and exercise in people with bronchiectasis: two different coins
Authors: Beatriz Herrero-Cortina, Arietta Spinou, Ana Oliveira, Brenda O'Neill, Cristina Jácome, Simone Dal Corso, William Poncin, Gerard Muñoz, Deniz Inal-Ince, Victoria Alcaraz-Serrano, Gregory Reychler, Angela Bellofiore, Annette Posthumus, James D. Chalmers, Annemarie L. Lee
Journal: European Respiratory Journal (2023)

For people with bronchiectasis, achieving long-term adherence to physiotherapy strategies is a major challenge. The regular use of airway clearance techniques (ACTs) reduces the burden of sputum-related symptoms ( e.g. increased expectoration during ACT session and reduced need to expectorate/cough throughout the rest of the day), improves quality of life and may reduce exacerbations, according to a recent European Respiratory Society statement [1]; however, there are barriers to long-term implementation (figure 1). There are traditional ( e.g. positioning, manual percussions and vibrations) and contemporary strategies ( e.g. breathing techniques and devices providing vibrations and/or positive or negative pressures) for airway clearance [1]. The selection of the most appropriate ACT for an individual patient is usually determined by respiratory physiotherapists, with selection based on clinical judgement and the patient's characteristics, symptoms, understanding and preferences [2]. Exercise and airway clearance techniques are two different coins, which when used together can make patients with bronchiectasis rich! https://bit.ly/3Lb7eyq
“Airway smooth muscle area to predict steroid responsiveness in COPD patients receiving triple therapy (HISTORIC): a randomised, placebo-controlled, double-blind, investigator-initiated trial.” D. Stolz, E. Papakonstantinou, M. Pascarella,<i>et al. Eur Respir J</i>2023; 62: 2300218.
Journal: European Respiratory Journal (2023)

In the Results: Secondary end-points: F ENO , residual volume, total lung capacity, health-related quality-of-life questionnaires section of the published version of this article, the data for the mean change in St George's Respiratory Questionnaire total score were transposed for the ACL/FOR/BUD and ACL/ FOR/placebo groups in the following sentence:In the group of patients with HASMC, the mean change of SGRQ total score was 8.58 (95% CI 1.19-15.96)for patients assigned to receive ACL/FOR/BUD and 0.67 (95% CI -6.90-8.28)for patients assigned to receive ACL/FOR/placebo, demonstrating a difference between the two medication groups >4 units, which is the minimum change of the score that indicates improvement in health-related quality of life.The correct version of the sentence should read as follows:In the group of patients with HASMC, the mean change of SGRQ total score was 8.58 (95% CI 1.19-15.96)for patients assigned to receive ACL/FOR/placebo and 0.67 (95% CI -6.90-8.28)for patients assigned to receive ACL/FOR/BUD, demonstrating a difference between the two medication groups >4 units, which is the minimum change of the score that indicates improvement in health-related quality of life.
Dynamic DNA methylation turnover in gene bodies is associated with enhanced gene expression plasticity in plants
Authors: Clara J. Williams, Dawei Dai, Kevin A. Tran, J. Grey Monroe, Ben P. Williams
Journal: Genome biology (2023)

In several eukaryotes, DNA methylation occurs within the coding regions of many genes, termed gene body methylation (GbM). Whereas the role of DNA methylation on the silencing of transposons and repetitive DNA is well understood, gene body methylation is not associated with transcriptional repression, and its biological importance remains unclear.We report a newly discovered type of GbM in plants, which is under constitutive addition and removal by dynamic methylation modifiers in all cells, including the germline. Methylation at Dynamic GbM genes is removed by the DRDD demethylation pathway and added by an unknown source of de novo methylation, most likely the maintenance methyltransferase MET1. We show that the Dynamic GbM state is present at homologous genes across divergent lineages spanning over 100 million years, indicating evolutionary conservation. We demonstrate that Dynamic GbM is tightly associated with the presence of a promoter or regulatory chromatin state within the gene body, in contrast to other gene body methylated genes. We find Dynamic GbM is associated with enhanced gene expression plasticity across development and diverse physiological conditions, whereas stably methylated GbM genes exhibit reduced plasticity. Dynamic GbM genes exhibit reduced dynamic range in drdd mutants, indicating a causal link between DNA demethylation and enhanced gene expression plasticity.We propose a new model for GbM in regulating gene expression plasticity, including a novel type of GbM in which increased gene expression plasticity is associated with the activity of DNA methylation writers and erasers and the enrichment of a regulatory chromatin state.
Metagenome-wide analysis uncovers gut microbial signatures and implicates taxon-specific functions in end-stage renal disease
Authors: Pan Zhang, Xifan Wang, Shenghui Li, Xuesen Cao, Jianzhou Zou, Yi Fang, Yiqin Shi, Fangfang Xiang, Bo Shen, Yixuan Li, Bing Fang, Yue Zhang, Ruochun Guo, Qingbo Lv, Liwen Zhang, Yufei Lu, Yaqiong Wang, Jinbo Yu, Yeqing Xie, Ran Wang, Xiaohong Chen, Jiawei Yu, Zhen Zhang, Jingjing He, Jing Zhan, Wenlv Lv, Yuxin Nie, Jieru Cai, Xialian Xu, Jiachang Hu, Qi Zhang, Ting Gao, Xiaotian Jiang, Xiao Tan, Ning Xue, Yimei Wang, Yimei Ren, Li Wang, Han Zhang, Yichun Ning, Jing Chen, Lin Zhang, Shi Jin, Fazheng Ren, Stanislav Dusko Ehrlich, Liang Zhao, Xiaoqiang Ding
Journal: Genome biology (2023)

The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
The landscape of cell-free mitochondrial DNA in liquid biopsy for cancer detection
Authors: Ymke van der Pol, Norbert Moldovan, Jip Ramaker, Sanne Bootsma, Kristiaan J. Lenos, Louis Vermeulen, Shahneen Sandhu, Idris Bahce, D. Michiel Pegtel, Stephen Q. Wong, Sarah-Jane Dawson, Dineika Chandrananda, Florent Mouliere
Journal: Genome biology (2023)

Abstract Background Existing methods to detect tumor signal in liquid biopsy have focused on the analysis of nuclear cell-free DNA (cfDNA). However, non-nuclear cfDNA and in particular mitochondrial DNA (mtDNA) has been understudied. We hypothesize that an increase in mtDNA in plasma could reflect the presence of cancer, and that leveraging cell-free mtDNA could enhance cancer detection. Results We survey 203 healthy and 664 cancer plasma samples from three collection centers covering 12 cancer types with whole genome sequencing to catalogue the plasma mtDNA fraction. The mtDNA fraction is increased in individuals with cholangiocarcinoma, colorectal, liver, pancreatic, or prostate cancer, in comparison to that in healthy individuals. We detect almost no increase of mtDNA fraction in individuals with other cancer types. The mtDNA fraction in plasma correlates with the cfDNA tumor fraction as determined by somatic mutations and/or copy number aberrations. However, the mtDNA fraction is also elevated in a fraction of patients without an apparent increase in tumor-derived cfDNA. A predictive model integrating mtDNA and copy number analysis increases the area under the curve (AUC) from 0.73 when using copy number alterations alone to an AUC of 0.81. Conclusions The mtDNA signal retrieved by whole genome sequencing has the potential to boost the detection of cancer when combined with other tumor-derived signals in liquid biopsies.
A fast non-parametric test of association for multiple traits
Authors: Diego Garrido-Martín, Miquel Calvo, Ferran Reverter, Roderic Guigó
Journal: Genome biology (2023)

Abstract The increasing availability of multidimensional phenotypic data in large cohorts of genotyped individuals requires efficient methods to identify genetic effects on multiple traits. Permutational multivariate analysis of variance (PERMANOVA) offers a powerful non-parametric approach. However, it relies on permutations to assess significance, which hinders the analysis of large datasets. Here, we derive the limiting null distribution of the PERMANOVA test statistic, providing a framework for the fast computation of asymptotic p values. Our asymptotic test presents controlled type I error and high power, often outperforming parametric approaches. We illustrate its applicability in the context of QTL mapping and GWAS.
Robust, scalable, and informative clustering for diverse biological networks
Authors: Chris Gaiteri, David R. Connell, Faraz A. Sultan, Artemis Iatrou, Bernard Ng, Boleslaw K. Szymanski, Ada Zhang, Shinya Tasaki
Journal: Genome biology (2023)

Abstract Clustering molecular data into informative groups is a primary step in extracting robust conclusions from big data. However, due to foundational issues in how they are defined and detected, such clusters are not always reliable, leading to unstable conclusions. We compare popular clustering algorithms across thousands of synthetic and real biological datasets, including a new consensus clustering algorithm—SpeakEasy2: Champagne. These tests identify trends in performance, show no single method is universally optimal, and allow us to examine factors behind variation in performance. Multiple metrics indicate SpeakEasy2 generally provides robust, scalable, and informative clusters for a range of applications.
Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma
Authors: Zhichao Liu, Yaru Zhang, Ning Ma, Yang Yang, Yunlong Ma, Feng Wang, Yan Wang, Jinzhi Wei, Hongyan Chen, Alfredo Tartarone, Jeffrey B. Velotta, Farshid Dayyani, Emmanuel Gabriel, Connor J. Wakefield, Biniam Kidane, Cristiano Carbonelli, Lingyun Long, Zhihua Liu, Jianzhong Su, Zhigang Li
Journal: Cancer Cell (2023)

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.
Frequency, morbidity and equity — the case for increased research on male fertility
Authors: Sarah Kimmins, Richard A. Anderson, Christopher L. R. Barratt, Hermann M. Behre, Sarah R. Catford, Christopher J. De Jonge, Geraldine Delbes, Michael L. Eisenberg, Nicolas Garrido, Brendan J. Houston, Niels Jørgensen, Csilla Krausz, Ariane Lismer, Robert I. McLachlan, Suks Minhas, Tim Moss, Allan Pacey, Lærke Priskorn, Stefan Schlatt, Jacquetta Trasler, Leonardo Trasande, Frank Tüttelmann, Mónica Hebe Vazquez-Levin, Joris A. Veltman, Feng Zhang, Moira K. O’Bryan
Journal: Nature Reviews Urology (2023)
The combination of Hebbian and predictive plasticity learns invariant object representations in deep sensory networks
Authors: Manu Srinath Halvagal, Friedemann Zenke
Journal: Nature Neuroscience (2023)

Abstract Recognition of objects from sensory stimuli is essential for survival. To that end, sensory networks in the brain must form object representations invariant to stimulus changes, such as size, orientation and context. Although Hebbian plasticity is known to shape sensory networks, it fails to create invariant object representations in computational models, raising the question of how the brain achieves such processing. In the present study, we show that combining Hebbian plasticity with a predictive form of plasticity leads to invariant representations in deep neural network models. We derive a local learning rule that generalizes to spiking neural networks and naturally accounts for several experimentally observed properties of synaptic plasticity, including metaplasticity and spike-timing-dependent plasticity. Finally, our model accurately captures neuronal selectivity changes observed in the primate inferotemporal cortex in response to altered visual experience. Thus, we provide a plausible normative theory emphasizing the importance of predictive plasticity mechanisms for successful representational learning.
<i>Notes from the Field:</i> Locally Acquired Mosquito-Transmitted (Autochthonous) <i>Plasmodium falciparum</i> Malaria — National Capital Region, Maryland, August 2023
Authors: Monique Duwell, Timothy DeVita, David Torpey, Jenny Chen, Robert A. Myers, Kimberly Mace, Alison D. Ridpath, Wycliffe Odongo, Brian H. Raphael, Audrey Lenhart, Jon Eric Tongren, Stephen Stanley, David Blythe
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

phpa/OIDEOR/CIDSOR/Pages/diseaseconditions-count-rates.aspx malaria exist in many areas in the United States (2).Locally acquired mosquito-transmitted (i.e., autochthonous) cases have not been identified since 2003; however, these imported cases represent a potential source of infection.In mid-2023, eight autochthonous malaria cases (Plasmodium vivax) were identified in Florida and Texas (3); in both states, the autochthonous cases occurred in the vicinity of an imported malaria case. Investigation and OutcomesOn August 6, a previously healthy resident of the Maryland National Capital Region was evaluated for a 7-day history of fever, malaise, and myalgias.In the months preceding symptom onset, the patient reported daily walks near home and an occurrence of a tick attachment but no international travel, blood transfusions, intravenous drug use, or other potential exposures to bloodborne pathogens.
Microsatellite Instability and Mismatch Repair Deficiency Define a Distinct Subset of Lung Cancers Characterized by Smoking Exposure, High Tumor Mutational Burden, and Recurrent Somatic MLH1 Inactivation
Authors: Soo-Ryum Yang, Erika Gedvilaite, Ryan Ptashkin, Jason Chang, John Ziegler, Douglas A. Mata, Liliana B. Villafania, Khedoudja Nafa, Jaclyn F. Hechtman, Ryma Benayed, Ahmet Zehir, Jamal Benhamida, Maria E. Arcila, Diana Mandelker, Charles M. Rudin, Paul K. Paik, Alexander Drilon, Adam J. Schoenfeld, Marc Ladanyi
Journal: Journal of Thoracic Oncology (2023)
Activity in primate visual cortex is minimally driven by spontaneous movements
Authors: Bharath Chandra Talluri, Incheol Kang, Adam Lazere, Katrina R. Quinn, Nicholas Kaliss, Jacob L. Yates, Daniel A. Butts, Hendrikje Nienborg
Journal: Nature Neuroscience (2023)

Organisms process sensory information in the context of their own moving bodies, an idea referred to as embodiment. This idea is important for developmental neuroscience, robotics and systems neuroscience. The mechanisms supporting embodiment are unknown, but a manifestation could be the observation in mice of brain-wide neuromodulation, including in the primary visual cortex, driven by task-irrelevant spontaneous body movements. We tested this hypothesis in macaque monkeys (Macaca mulatta), a primate model for human vision, by simultaneously recording visual cortex activity and facial and body movements. We also sought a direct comparison using an analogous approach to those used in mouse studies. Here we found that activity in the primate visual cortex (V1, V2 and V3/V3A) was associated with the animals' own movements, but this modulation was largely explained by the impact of the movements on the retinal image, that is, by changes in visual input. These results indicate that visual cortex in primates is minimally driven by spontaneous movements and may reflect species-specific sensorimotor strategies.
Improving radiotherapy in immunosuppressive microenvironments by targeting complement receptor C5aR1
Authors: Callum Beach, David MacLean, Dominika Majorova, Stavros Melemenidis, Dhanya K. Nambiar, Ryan K. Kim, Gabriel N. Valbuena, Silvia Guglietta, Carsten Krieg, Mahnaz Darvish-Damavandi, Tatsuya Suwa, Alistair Easton, Lily V.S. Hillson, Ashley K. McCulloch, Ross K. McMahon, Kathryn Pennel, Joanne Edwards, Sean M. O’Cathail, Campbell S. Roxburgh, Enric Domingo, Eui Jung Moon, Dadi Jiang, Yanyan Jiang, Qingyang Zhang, Albert C. Koong, Trent M. Woodruff, Edward E. Graves, Tim Maughan, Simon J.A. Buczacki, Manuel Stucki, Quynh-Thu Le, Simon J. Leedham, Amato J. Giaccia, Monica M. Olcina
Journal: Journal of Clinical Investigation (2023)

An immunosuppressive microenvironment causes poor tumor T cell infiltration and is associated with reduced patient overall survival in colorectal cancer. How to improve treatment responses in these tumors is still a challenge. Using an integrated screening approach to identify cancer-specific vulnerabilities, we identified complement receptor C5aR1 as a druggable target, which when inhibited improved radiotherapy, even in tumors displaying immunosuppressive features and poor CD8+ T cell infiltration. While C5aR1 is well-known for its role in the immune compartment, we found that C5aR1 is also robustly expressed on malignant epithelial cells, highlighting potential tumor cell-specific functions. C5aR1 targeting resulted in increased NF-κB-dependent apoptosis specifically in tumors and not normal tissues, indicating that, in malignant cells, C5aR1 primarily regulated cell fate. Collectively, these data revealed that increased complement gene expression is part of the stress response mounted by irradiated tumors and that targeting C5aR1 could improve radiotherapy, even in tumors displaying immunosuppressive features.
Prevalence of Diagnosed Arthritis — United States, 2019–2021
Authors: Elizabeth A. Fallon, Michael A. Boring, Anika L. Foster, Ellen W. Stowe, Tyler D. Lites, Erica L. Odom, Puja Seth
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Arthritis includes approximately 100 conditions that affect the joints and surrounding tissues. It is a leading cause of activity limitations, disability, and chronic pain, and is associated with dispensed opioid prescriptions, substantially contributing to health care costs. Combined 2019-2021 National Health Interview Survey data were analyzed to update national prevalence estimates of self-reported diagnosed arthritis. An estimated 21.2% (18.7% age-standardized) of U.S. adults aged ≥18 years (53.2 million) had diagnosed arthritis during this time frame. Age-standardized arthritis prevalences were higher among women (20.9%) than men (16.3%), among veterans (24.2%) than nonveterans (18.5%), and among non-Hispanic White (20.1%) than among Hispanic or Latino (14.7%) or non-Hispanic Asian adults (10.3%). Adults aged ≥45 years represent 88.3% of all U.S. adults with arthritis. Unadjusted arthritis prevalence was high among adults with chronic obstructive pulmonary disease (COPD) (57.6%), dementia (55.9%), a disability (54.8%), stroke (52.6%), heart disease (51.5%), diabetes (43.1%), or cancer (43.1%). Approximately one half of adults aged ≥65 years with COPD, dementia, stroke, heart disease, diabetes, or cancer also had a diagnosis of arthritis. These prevalence estimates can be used to guide public health policies and activities to increase equitable access to physical activity opportunities within the built environment and other arthritis-appropriate, evidence-based interventions.
Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation
Authors: Boa Kim, Wencao Zhao, Soon Y. Tang, Michael G. Levin, Ayon Ibrahim, Yifan Yang, Emilia Roberts, Ling Lai, Jian Li, Richard K. Assoian, Garret A. FitzGerald, Zoltan Arany
Journal: Journal of Clinical Investigation (2023)

The metabolic syndrome, today affecting more than 20% of the US population, is a group of five conditions that often co-exist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism, and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo, and blunts blood pressure elevation in response to high fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.